A fundamental feature of cortical neurons is the way they transform input current into action potential output. Many cortical neurons adapt: the interval between successive action potentials increases in response to constant current injection. The ion channels mediating this behavior have been sought for more than two decades. We discovered that corticospinal neurons in motor cortex have the opposite behavior: the interval between successive action potentials decreases. The mechanisms of this firing rate acceleration are also not known. We have used microarrays to profile gene expression in distinct populations of cortical neurons. These experiments have identified potassium channels that may underlie adaptation and acceleration. Here we will test the role of these channels in endowing cortical cell types with distinct firing properties. We will determine how firing properties differ across anatomically and genetically defined cell types and how these properties vary across cortical regions. We will also study the emergence of cell type specific firing properties during development, and determine whether or not the development and maintenance of intrinsic firing properties is activity dependent. Significance: Cortical circuits malfunction in epilepsy, stroke and developmental disorders such as mental retardation and autism. Understanding the molecular and physiological properties that distinguish different classes of neurons that make up cortical circuits may illuminate the malfunction of these circuits during disease. [unreadable] [unreadable] [unreadable]